The invention relates to an optical diagnosis system for small animal imaging, in which the animal which has been arranged on a bearing plate and treated with an activatable optical contrast medium is irradiated by an excitation source and the resulting fluorescent radiation that is radiated back is detected by means of a detector system.
In examinations of metabolic functions on a living small animal, use is made of activatable optical contrast media which fluoresce in the near infrared. The contrast medium is inert in healthy tissue and is activated, that is to say transferred into a fluorescent state, only in the target tissue, for example a tumor, by illness-correlated metabolic activities (enzymatic processes). Through a highly selective activation mechanism, a very high signal-to-noise ratio is achieved with this contrast medium. The metabolic activity can be quantified by measurement after determination of the activation rate. However, this requires knowledge not only of the concentration of the activated contrast medium that is to be determined by the fluorescent signal but also of the initial concentration of the inert contrast medium in the target tissue. This value cannot be calculated from the injected dose, but rather has to be determined experimentally, which can preferably be effected by a second continuously signaling marker which does not interfere with the activation signal, such as a radioisotope marker, for example. Such a method presupposes a dual imaging, in which case, hitherto, after the determination of the activated contrast medium by measurement of the fluorescent radiation, the animal has first had to be transferred into a second imaging system, in order to detect the second continuously signaling marker of the contrast medium. In addition to the additional burden imposed by this repositioning of the animal, which can lead to considerable health problems, these measurements in two different imaging systems make the superposition of the two images more difficult, since artificial or anatomic markers have to be used for the registration. Furthermore, the measurement accuracy is impaired, particularly in the case of parameters that fluctuate greatly with respect to time in the target tissue (high enzymatic conversion and fast pharmacodynamics).
The invention is therefore based on the object of configuring an optical diagnosis system of the type mentioned in the introduction in such a way that working with two imaging systems between which the animal has to be transferred is obviated.
In order to achieve this object, the invention provides for the bearing plate to be designed as a radiation-transparent window for a reference radiationxe2x80x94generated by a second marker of the contrast mediumxe2x80x94for the detection of the initial concentration of the inert contrast medium.
According to the invention, then, the optical diagnosis system is designed in such a way thatxe2x80x94through a coupling by means of the bearing plate designed as a radiation-transparent windowxe2x80x94the imaging system for the second continuously signaling marker is integrated into the imaging system for the fluorescent radiation. This enables simultaneous measurement both of the fluorescent radiation and of the reference radiation, thereby producing a very high measurement accuracy, in conjunction with the simple registration of the two images, since, after all, they are in each case recorded with the same positioning of the animal.
The second marker could also be formed, in principle, by a second fluorescent marker for the inert contrast medium with an altered frequency. Preferably, however, the second marker is intended to be a radioisotope marker, the window, below which a gamma ray receiver is arranged, being gamma-ray-transmissive, but preferably NIR-opaque.
Such a window may comprise, for example, thin aluminum sheet or, alternatively, carbon fiber reinforced plastic.
The fluorescent radiation of the excitation source, which may be an infrared laser diode, for example, may be excitable and measurable in different directions in order to obtain 3D information, in which case depth information can be calculated from the measured values of at least two different reception angles. This can be effected automatically in the device by means of a corresponding algorithm and a corresponding design of the evaluation electronics.